配对关联经颅磁刺激治疗言语失用患者听觉反馈调控障碍的神经机制研究

Apraxia of speech (AOS) is a typical speech disorder of stroke patients with aphasia. However, the current treatment is less effective, which suggests that there might be other mechanisms underlying the development of AOS. Our previous studies have showed that auditory feedback plays an important role in the online control of human speech and vocalization, and AOS patients have been observed with frequent and effortful attempts to self-correct articulatory errors. Therefore, it would be reasonable to hypothesize that the auditory feedback control is impaired in the AOS patients. And the reduced connections between individual cortical areas within the neural network probably attributes to the impaired auditory feedback control. Our present study attempts to stimulate the superior temporal gyrus (STG) and the Sylvian-Parietal-temporal area (Spt) using paired associative transcranial magnetic stimulation, in order to induce the long-term-potentiation-like plasticity of auditory cortex and enhance the activation coherence between STG and Spt. It may not only repair the neural network of auditory feedback control but also improve the theraputic effectiveness of AOS. The results of this project are expected to validate the defects of auditory feedback control in AOS, and provide a controllable and targeting paradigm of non-invasive brain stimulation to remediate a variety of motor speech disorders.

言语失用是脑卒中后失语症患者常见的一种言语功能障碍，但治疗效果欠佳，提示可能存在未知的发病机制，应用现有的治疗方法不能产生针对性的作用。我们的前期研究表明，听觉反馈对言语发声运动具有重要的调控作用，而临床观察发现，言语失用患者有频繁且费力的自我纠正以及言语停顿等特征，我们据此作出假设：言语失用患者存在听觉反馈调控障碍，而听觉反馈神经调控网络纤维连接受损可能是产生功能障碍的主要原因。本项目拟对言语失用患者的听觉反馈调控能力进行探讨，利用配对关联刺激模式对颞上回（STG）和大脑外侧裂、顶、颞叶交界（Spt）这两个听觉反馈调控网络中的重要脑区进行经颅磁刺激（TMS），诱导听觉皮层出现长时程增强样的可塑性改变，增加脑区间激活的协同性，实现修复听觉反馈神经网络连接的目的。本项目有望进一步揭示言语失用的发病机制，为言语康复提供一种可控性好、靶向性强的非侵入性脑刺激治疗方式。

言语失用是脑卒中后失语症患者常见的一种神经性言语功能障碍，是感觉运动的计划及编码阶段缺陷，不能产生恰当的动作并得到具有正确音素和正常节律的语音。言语失用患者有频繁且费力的自我纠正以及言语停顿等特征，可能同时存在听觉反馈调控障碍。本课题针对言语失用患者的听觉反馈调控能力和运动编码阶段的功能障碍，结合行为学、声学及事件相关电位（Event‐related Potential，ERP）等方法与技术，对配对关联经颅磁刺激（Transcranial Magnetic Stimulation，TMS）治疗言语失用患者、诱导皮层出现正常化可塑性改变的神经机制进行了初步研究。首先通过听觉反馈基频扰动技术定量测量了言语失用患者的听觉反馈调控能力，进而设计了一个模拟言语感知训练程序，诱导听觉-发声运动整合机制产生可塑性改变。在此基础上课题组对言语失用患者采用图片命名联合TMS的治疗方法，在出声命名的运动计划编码阶段，对患者的听觉皮层施加高频配对TMS。结果显示，治疗后言语失用患者汉语标准失语症评估名词和动词的口语命名正答率较前提高，反应时间缩短，命名任务的ERP检测显示言语失用患者运动计划阶段的脑电反应趋于正常化，平均电位与正常对照组相比差异较前明显缩小，推测言语失用患者口语表达时听觉反馈的参与增多，有利于建立可靠的前馈信息，从而提高了命名前运动计划的编码效率。综合上述结果，本研究为言语康复的非侵入性靶向脑刺激治疗方式奠定了工作基础，同时为进一步揭示言语失用的发病机制提供了线索。